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Keywords:

  • air pollution;
  • chronic obstructive pulmonary disease;
  • emphysema;
  • non-smoking

ABSTRACT

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. PREVALENCE OF COPD IN NON-SMOKERS
  5. RISK FACTORS OF COPD IN NON-SMOKERS
  6. CLINICAL FEATURES AND PHENOTYPES OF NON-SMOKING-RELATED COPD
  7. CONCLUSION
  8. REFERENCES

Chronic obstructive pulmonary disease (COPD) is an increasing cause of morbidity and mortality worldwide, and it has been strongly correlated to tobacco smoking. While a number of studies have concentrated on smokers only, recent published data demonstrate that at least one fourth of patients with COPD are non-smokers, and that the burden of COPD in non-smokers is also higher than previously believed. Risk factors of COPD in non-smokers may include genetic factors, long-standing asthma, outdoor air pollution (from traffic and other sources), environmental smoke exposure (ETS), biomass smoke, occupational exposure, diet, recurrent respiratory infection in early childhood, tuberculosis and so on. In Asian region, indoor/outdoor air pollution and poor socioeconomic status may play important roles in the pathogenesis of non-smoking-related COPD. The prevalence of COPD among never smokers varies widely across nations. Such a variation may arise from several aspects, including study design, definition of COPD, diagnostic criteria, age and gender distribution of the studied population, local risk factors and socioeconomic status. More investigations and efforts are required to elucidate the involved factors and their shared contributions to non-smoking-related COPD so as to achieve better estimation and reduction of the burden of this neglected entity worldwide.


INTRODUCTION

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. PREVALENCE OF COPD IN NON-SMOKERS
  5. RISK FACTORS OF COPD IN NON-SMOKERS
  6. CLINICAL FEATURES AND PHENOTYPES OF NON-SMOKING-RELATED COPD
  7. CONCLUSION
  8. REFERENCES

Chronic obstructive pulmonary disease (COPD), a process characterized by the presence of chronic bronchitis or emphysema that may lead to the development of airway obstruction,1 is an important and increasing cause of morbidity and mortality throughout the world.2–4 COPD is projected to rank third among all causes of death by 2020.5

Traditionally, tobacco smoking is linked to COPD since the 1950s6 and has long been widely known as the single most important risk factor for COPD. A great percentage of COPD mortality in both genders can be attributed to cigarette smoking.7 Because of such a well-documented association, a number of studies have concentrated on the role of smoking in COPD, focusing only on smokers,8 in particular, those with at least 20 pack-years of cigarette smoking exposure. However, published data in recent years demonstrate a significant prevalence of COPD among never smokers with varying prevalence across nations. While the burden of non-smoking-related COPD is higher than previously believed in both developed and developing countries,9 little is known about the picture of COPD in non-smokers. In a study by Lamprecht and colleagues, 81.2% of never smokers with moderate to severe airway obstruction were previously undiagnosed.10 This clearly reflects the lack of recognition and underdiagnosis of non-smoking-related COPD, possibly as a result of little knowledge on this condition, as well as poor understanding and appreciation of risk factors other than smoking. This paper aims to increase the awareness of non-smoking-related COPD and to call for future studies and medication attention to this patient population.

PREVALENCE OF COPD IN NON-SMOKERS

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. PREVALENCE OF COPD IN NON-SMOKERS
  5. RISK FACTORS OF COPD IN NON-SMOKERS
  6. CLINICAL FEATURES AND PHENOTYPES OF NON-SMOKING-RELATED COPD
  7. CONCLUSION
  8. REFERENCES

Cigarette smoking causes COPD in 50–70% of patients even in developed countries. Indeed, the Obstructive Lung Disease in Northern Sweden (OLIN) and US National Health and Nutrition Examination Survey (NHANES) III studies reported that the population attributable risk of COPD from smoking in these countries were 45% and 44%, respectively.11,12 Increasing evidence indicate that non-smokers may account for between one fourth and one third of all COPD cases.13–18 A recent review from Salvi and Barnes9 showed that the proportion of non-smoking-related COPD in all COPD cases ranged from 17.0% in Venezuela to 68.6% in India, depending on a wide diversity of studied population and the definition of COPD. The proportion appears higher in developing countries and lower in developed countries. For instance, 47.6% of patients with COPD identified by a respiratory questionnaire in South Africa19 are non-smokers and the figure goes to 68.6% in India10 but falls to 17.0% in 16 developed countries,20 20.0% in Sweden,21 and 20.2% in Finland,22 respectively. Based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometry criteria, an estimated 17.0–38.8% of patients with COPD were non-smokers worldwide, with 23% in USA,13 22.9% in UK,23 and 23.4% in Spain.24 In Chinese Epidemiological Survey of COPD (CESCOPD) study, the prevalence of COPD according to GOLD diagnostic criteria among non-smokers aged 40 years or older was 5.2%,25 and non-smokers account for 38.6% of all COPD patients.26

As illustrated earlier, prevalence of COPD among non-smokers showed significant variation across geographic regions and epidemiological studies. Such a variation may arise from several aspects, including study design, definition of COPD, diagnostic criteria (GOLD spirometrically confirmed vs self-report), age and gender distribution of the studied population,27 presence of risk factors (second-hand smoke, tuberculosis, indoor air pollution, etc.) other than smoking19,28 and socio-economic status (SES). More efforts are warranted in future COPD studies to control for these confounders, so as to provide better comparison of COPD rates in different populations of non-smokers. Nevertheless, currently available data suggest that the burden caused by non-smoking-related COPD is much higher than previously expected in both developed and developing countries,29 and that risk factors other than cigarette smoking may contribute to higher prevalence of non-smoking-related COPD in developing countries than that in developed countries.30

RISK FACTORS OF COPD IN NON-SMOKERS

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. PREVALENCE OF COPD IN NON-SMOKERS
  5. RISK FACTORS OF COPD IN NON-SMOKERS
  6. CLINICAL FEATURES AND PHENOTYPES OF NON-SMOKING-RELATED COPD
  7. CONCLUSION
  8. REFERENCES

Risk factors in non-smokers may include genetic factors, long-standing asthma, outdoor air pollution (from traffic and other sources), environmental smoke exposure (ETS), biomass smoke, occupational exposure, diet, recurrent respiratory infection in early childhood, tuberculosis and so on. In the Asian region, indoor and outdoor air pollution and poor SES may play important roles in the pathogenesis of COPD in non-smokers.

Indoor air pollution

Sources of indoor air pollution mainly include coal and biomass fuel combustion, as well as ETS.

Biomass fuels such as wood, charcoal, crops, twigs, dry grass and dung are widely used for cooking or heating in low-income countries.31 According to the World Health Organization estimation, approximately 50% of all households and 90% of rural households utilize biomass or coal fuels for cooking and heating in the world. About three billion people worldwide are exposed to smoke produced from biomass or coal fuel burning. In China, approximately 60% of rural households use biomass fuel for cooking and 31% use coal fuel.32 In recent investigations involving 13 urban and rural areas in China, 44.6% and 73.2% of non-smokers had been reported to be exposed to biomass and coal smoke, respectively, and 40% had poor ventilation in the kitchen.29

A cluster disproportional random sampling survey was performed in populations aged over 40 years in urban (Liwang) and rural (Yunyan) areas in Guangdong, China.33 The overall prevalence of COPD in the two areas (Liwang and Yunyan) was 9.4%. The prevalence of COPD in non-smoking women in rural Yunyan was significantly higher than in urban Liwang (7.2% vs 2.5%). The use of biomass fuel was higher in rural Yunyan than in urban Liwang (88.1% vs 0.7%). Univariate analysis showed a significant association between COPD and exposure to biomass fuel for cooking. Multivariate analysis showed a positive association between COPD and urban/rural area (surrogate for fuel type and local exhaust ventilation in kitchen).

ETS is another major contributor to indoor air pollution apart from biomass and coal smoke. In China, the prevalence of ETS is much higher34 because there is little restriction on smoking in public indoor places. Gu et al.35 reported that 49.2% of non-smokers aged 35–74 years had been exposed to ETS at home or in the workplace, with 12.1% of men and 51.3% of women at home, and 26.7% of men and 26.2% of women in their workplaces. A study in Guangzhou34 reported that 28% of women had ETS exposure 40 h per week in more than 5 years. In our recent national surveys,29 78.2% of non-smokers at the age of 40 years or older had ETS exposure.

Previous literature indicated that ETS was associated with an increase in the risk of both acute respiratory illness among children and chronic respiratory disease among adults.36,37 Studies have also suggested that women are more susceptible to the effects of tobacco smoke.38,39 In China, Yin et al.34 showed a link between ETS exposure and the risk of COPD among non-smokers. There was an association between the risk of COPD and self-reported exposure to ETS at home and the workplace with 1.48 (95% confidence interval: 1.18–1.85) of an adjusted odds ratio for high-level exposure (equivalent to 40 h a week for more than 5 years), and there were significant associations between reported respiratory symptoms and increasing ETS exposure (1.16, 1.07–1.25 for any symptom). Over 60% of the Chinese adults are non-smokers40, and according to an investigation by Yin et al.,34 about 1.9 million deaths from non-smoking-related COPD could be attributed to ETS in the current population in China. Thus, legislations or regulations preventing passive smoking are urgent in China.

Outdoor air pollution

The association between high concentrations of outdoor air pollutants and COPD exacerbations and worsening of pre-existing COPD is supported by strong evidence.41 Longitudinal cohort studies provide strong evidence of an association between outdoor pollution and decreased pulmonary function growth during childhood and adolescence.42–44

Recently, a global air pollution survey by World Health Organization45 showed that among 1085 cities being surveyed, most of the cities from India, China, Pakistan, Mongolia and Indonesia are ranked in a World Health Organization-released database46 as heavy air-polluted cities (annual mean particulate matter 10 or PM10>100 µg/m3). Ko F.W. et al.47 reported that once PM10 increased by each 10 µg/m3, the hospitalization rate of COPD acute exacerbation increased by 2.4% (or 3.1% by the increase of 10 PM2.5 µg/m3). In a recent 4-year study in China, the data suggested that subjects with an improvement on outdoor air pollution had less decline of forced expiratory volume in 1 s than those living in a relatively worse environment.48

Poor SES

Yin et al. used nationwide data from China Chronic Disease Risk Factor Surveillance in 2007 to estimate the prevalence of self-reported physician-diagnosed COPD and to examine its association with SES.49 Of 51 520 subjects sampled from 31 provinces, autonomous regions and municipalities, 49 363 subjects with complete data were included in the analysis in this report. Both low educational attainment and low household income were independently associated with higher risk of physician-diagnosed COPD. Among never smokers, low educational level and household income were still associated with a significant higher prevalence of COPD (odds ratio 1.77, 95% confidence interval: 1.40–2.25, odds ratio 1.31, 95% confidence interval: 1.05–1.62). Thus, SES is a risk factor for self-reported physician-diagnosed COPD independently of current or passive smoking. Mechanism explaining the adverse effects of low SES on COPD among never smokers might be poor dietary habits (low in anti-oxidants and fresh fruit),50 poor housing conditions,51 more occupational dust exposure and indoor air pollution from biomass combustion in low SES group.52

CLINICAL FEATURES AND PHENOTYPES OF NON-SMOKING-RELATED COPD

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. PREVALENCE OF COPD IN NON-SMOKERS
  5. RISK FACTORS OF COPD IN NON-SMOKERS
  6. CLINICAL FEATURES AND PHENOTYPES OF NON-SMOKING-RELATED COPD
  7. CONCLUSION
  8. REFERENCES

Moran-Mendoza et al.53 reported that women with COPD due to exposure to biomass smoke had more lung fibrosis, greater pigment deposition and thicker pulmonary artery intimae than did those with COPD due to tobacco smoking, who had greater emphysema and epithelial damage. Ozbay et al.54 investigated the high-resolution CT findings in non-smoking COPD women. The results suggested that biomass fuel has deleterious effects on pulmonary function and structure leading to obstructive and restrictive pathologies. However, Ramírez-Venegas et al.55 reported that Mexican women who had COPD and had been exposed to smoke from biomass fuel had similar clinical characteristics, quality of life and mortality to those with COPD due to tobacco smoking. The study in China29 indicated that COPD may have different profiles between smokers and non-smokers. Unlike those with smoking-related COPD, non-smoking COPD patients were less likely to have respiratory symptoms including chronic cough and expectoration, lower BMI, lower forced expiratory volume in 1 s/forced vital capacity ratio and forced expiratory volume in 1 s percentage predicted values and previous medical records of chronic bronchitis or COPD, while were more likely to have asthma diagnosed by a physician and most had suffered respiratory diseases in their childhood. As a result, patients with non-smoking-related COPD were often ignored or underdiagnosed, in particular during the mild or moderate stage of the disease.

CONCLUSION

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. PREVALENCE OF COPD IN NON-SMOKERS
  5. RISK FACTORS OF COPD IN NON-SMOKERS
  6. CLINICAL FEATURES AND PHENOTYPES OF NON-SMOKING-RELATED COPD
  7. CONCLUSION
  8. REFERENCES

At least one fourth of patients with COPD are non-smokers, but little is known about the picture of COPD in this neglected population, and the burden of COPD in non-smokers is also higher than previously believed. While the prevalence of COPD in this subgroup varies across nations and studies, possibly resulting from a combination of reasons, non-smoking-related COPD affects more people in developing countries than it does in developed countries. Therefore, increased awareness and understanding of other factors that may cause COPD are needed. Further investigations are required to elucidate the involved factors and their shared contributions to this disease to achieve better estimation and reduction of the burden of non-smoking-related COPD worldwide.

REFERENCES

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. PREVALENCE OF COPD IN NON-SMOKERS
  5. RISK FACTORS OF COPD IN NON-SMOKERS
  6. CLINICAL FEATURES AND PHENOTYPES OF NON-SMOKING-RELATED COPD
  7. CONCLUSION
  8. REFERENCES
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